year: 1974
started with a patient with familial hypercholesterolaemia which is found in one in a million within the population.
goldstein and brown found that in this patients fibroblasts, there was an overactivity of HMG CoA reductase
they then showed the role of LDL binding to high affinity receptors and becoming degraded and suppression of HMG CoA reductase
tthey concluded that high affinity binding of LDL normally results in endocytosis and lysosomal degradation of LDL and that cholestreol released during this process leads to inhibition of HMG CoA reductase
this is how they then earnt their nobel prize